Mutations in the paralogous human alpha-globin genes yielding identical hemoglobin variants. 2009

Kamran Moradkhani, and Claude Préhu, and John Old, and Shirley Henderson, and Vera Balamitsa, and Hong-Yuan Luo, and Man-Chiu Poon, and David H K Chui, and Henri Wajcman, and George P Patrinos
Biochimie Génétique, AP-HP, Hôpital Henri Mondor, Créteil, France.

The human alpha-globin genes are paralogues, sharing a high degree of DNA sequence similarity and producing an identical alpha-globin chain. Over half of the alpha-globin structural variants reported to date are only characterized at the amino acid level. It is likely that a fraction of these variants, with phenotypes differing from one observation to another, may be due to the same mutation but on a different alpha-globin gene. There have been very few previous examples of hemoglobin variants that can be found at both HBA1 and HBA2 genes. Here, we report the results of a systematic multicenter study in a large multiethnic population to identify such variants and to analyze their differences from a functional and evolutionary perspective. We identified 14 different Hb variants resulting from identical mutations on either one of the two human alpha-globin paralogue genes. We also showed that the average percentage of hemoglobin variants due to a HBA2 gene mutation (alpha2) is higher than the percentage of hemoglobin variants due to the same HBA1 gene mutation (alpha1) and that the alpha2/alpha1 ratio varied between variants. These alpha-globin chain variants have most likely occurred via recurrent mutations, gene conversion events, or both. Based on these data, we propose a nomenclature for hemoglobin variants that fall into this category.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D006454 Hemoglobins The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Eryhem,Ferrous Hemoglobin,Hemoglobin,Hemoglobin, Ferrous
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014644 Genetic Variation Genotypic differences observed among individuals in a population. Genetic Diversity,Variation, Genetic,Diversity, Genetic,Diversities, Genetic,Genetic Diversities,Genetic Variations,Variations, Genetic
D017085 alpha-Thalassemia A disorder characterized by reduced synthesis of the alpha chains of hemoglobin. The severity of this condition can vary from mild anemia to death, depending on the number of genes deleted. Hemoglobin H Disease,Thalassemia-alpha,A-Thalassemia,Alpha Thalassemia,Disease, Hemoglobin H,Thalassemia alpha,Thalassemia, Alpha,alpha-Thalassemias
D055542 alpha-Globins Members of the alpha-globin family. In humans, they are encoded in a gene cluster on CHROMOSOME 16. They include zeta-globin and alpha-globin. There are also pseudogenes of zeta (theta-zeta) and alpha (theta-alpha) in the cluster. Adult HEMOGLOBIN is comprised of 2 alpha-globin chains and 2 beta-globin chains. alpha-Globin,alpha 1-globin,alpha-1 Globin,alpha-2 Globin,1-globin, alpha,Globin, alpha-1,Globin, alpha-2,alpha 1 Globin,alpha 2 Globin,alpha Globin,alpha Globins

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